The complement system is one of the evolutionary ancient, primordial components of the immune system. As such, it was destined to fulfill most aspects of the immune response with built-in self-limiting regulatory components. While new and new layers of immune repertoire evolved, complement retained its influential role in recognition, phagocytosis, clearance, antibody diversity, adaptive immune response and regulation. In essence the complement system is an innate patent recognition niché, serving to process pathogens, clearing debris and to condition adaptive immunity. The three complement amplification pathways are individually or in combination regulated by soluble and membrane bound complement regulators, Regulator of Complement Activation (RCAs). Among them Complement Regulator-1(CR1) stands out for diversity of functions, and may be of particular interest for intensivists beyond complement regulatory roles, the emergence of regulatory T cells, a more complex executive function, due to erythrocyte bound clearance mechanisms, to aiding opsonophagocytosis of pathogens, and increasing affinity maturation of monoclonal antibodies. This review article sets out to describe CR1, bridging basic science, with behavior in intensive care related clinical scenarios, that are typically associated with a Systemic Inflammatory Response (SIRS), in which complement is involved by direct engagement or indirectly, in situations when opportunities of modifications have a real potential.